Ozone and acid fog and acid rain (including sulfuric acid aerosols) are of major public health concern, in part because they are capable of producing measurable transient effects on the lungs of susceptible subjects, at concentrations which can occur in ambient pollutant episodes, and in part because they may act synergistically to produce effects on the lung greater than that produced by individual exposures. Knowledge concerning the possible deleterious effects of ozone-acid synargisms on the respiratory tract is still extremely meager. A sheep model system is proposed to examine the synergistic effect between ozone and respirable-sized sulfuric acid aerosols. In the current study we will use a multidisciplinary approach designed to evaluate the effects of ozone, acid aerosol, and their combination, on respiratory tract epithelial and endothelial permeability. Bronchoalveolar clearance of 99mTc-DTPA radioaersol from the lung will be used to determine epithelial permeability and results obtained will be compared to appearances of protein, lysosomal enzymes and cells in bronchoalveolar lavage carried out via a standard methodology. Sheep lung lymph will obtained to evaluate endothelial permeability and possible clearances of 99mTc-DTPA via lung lymphatics. Finally, in a separate series of sheep exposed to an identical protocol of ozone, acid aerosol or combined ozone-acid aerosol, airway blood flow will be continuously monitored using a Doppler flowmeter-telemetry system. Changes in airway blood flow are expected to provide an index of neurogenic or mediator- related events occurring in airway interstitium and which would be expected to effect airway smooth muscle as well as airway microvasculature. In subsequent years we plan to specifically examine for the role(s) of oxy radical productions (and other potential mediators) on this synergism via uses of various infused and aerosolized quenching agents and radical scavengers as in vivo antagonists.